A novel mutation in complement 2 accompanied by susceptibility variants in C3 glomerulonephritis: A case study

Area of Science:

• Nephrology
• Genetics
• Immunology

Background:

• C3 glomerulonephritis is a rare chronic kidney disease linked to alternative complement pathway dysregulation.
• It is characterized by C3c-dominant deposition on kidney biopsies.

Observation:

• A 36-year-old man presented with nephritic syndrome and normal renal function.
• Renal biopsy showed a membranoproliferative glomerulonephritis pattern consistent with C3 glomerulonephritis.
• Genetic screening revealed susceptibility variants in complement factor H and thrombomodulin, and a novel variant in complement 2.

Findings:

• The patient lacked autoantibodies but carried genetic variants increasing susceptibility to complement-mediated diseases and infection risk.
• A novel complement 2 variant may contribute to C3 glomerulonephritis development in conjunction with other susceptibility variants.
• Treatment with ramipril and fresh frozen plasma resulted in controlled proteinuria and stable renal function.

Implications:

• This case underscores the multifactorial etiology of C3 glomerulopathy, involving genetic predisposition and environmental triggers.
• Understanding the interplay of genetic variants and triggers is crucial for diagnosing and managing C3 glomerulonephritis.
• The findings suggest a combined genetic and trigger-based approach to understanding C3 glomerulonephritis pathogenesis.